新型单克隆抗体对皮下血管瘤细胞的抑制作用及其机制  

Inhibitory effect and mechanism of novel monoclonal antibody on subcutaneous hemangioma cells

作　　者：黄崇青[1] 虞冠锋[1] 黄景勇[1] 麻朋艳[1] 万丽[2] Huang Chongqing;Yu Guanfeng;Huang Jingyong;Ma Pengyan;Wan Li(Department of Vascular Surgery, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325015, China （Huang CQ, Yu GF, Huang JY, Ma PY;Department of Pathology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325015, China （ Wan L)

机构地区：[1]温州医科大学附属第一医院血管外科,325015 [2]温州医科大学附属第一医院病理科,325015

出　　处：《中华实验外科杂志》2018年第7期1218-1221,共4页Chinese Journal of Experimental Surgery

基　　金：温州市公益性社会发展科技项目（Y20160407）

摘　　要：目的探讨一种新型单克隆抗体（FAB）雷珠单抗（Ranibizumab）抑制裸鼠皮下结缔组织血管瘤的疗效及其机制，研究药物使用的最佳配方。方法血管瘤细胞注射法建立动物实验模型，分别使用无药物治疗、注射0．25、0．50、0．75mg/cm^3浓度的雷珠单抗、1mg／cm^3的平阳霉素、0．75mg／cm^3雷珠单抗＋10ng／cm^3的类胰岛素生长因子（IGF-1）、0．75mg／cm^3雷珠单抗＋30ng／cm^3的丙二醇甲醚醋酸酯（PMA），分为A（基础对照）、B、C、D、E（药物对照）、F（雷珠单抗＋IGF-1）、G（雷珠单抗＋PMA）组。运用组织细胞学和分子生物学检测手段，验证疗效及机制。结果各药物治疗2周后，血管瘤体积均有减小[A组：（171．76±52．46）mm^3，B组：（70．85±8．73）mm^3，C组：（69．84±16．33）mm^3，D组：（41．83±18．65）mm^3，E组：（61．52±8．12）mm^3，F组：（103．41±19．33）mm^3和G组：（101．19±57．51）mm^3，P=0．001]。不同药物治疗组裸鼠血管瘤组织中CD34和Ki-67的蛋白表达明显下降。除了雷珠单抗合用IGF-1治疗组外，其余组各组裸鼠肺组织受到不同程度的损伤，但各雷珠单抗治疗组对于肺组织的损伤要轻于平阳霉素。雷珠单抗明确抑制裸鼠肿瘤组织中血管内皮生长因子A（VEGF—A）的蛋白表达，导致组织细胞凋亡。在接受雷珠单抗治疗的同时，采用IGF-1干预下，能维持胞内磷脂酰肌醇激酶／赁白激酶B（P13K／Akt）信号通路，保护肺组织细胞。结论雷珠单抗通过抑制肿瘤组织中VEGF—A的蛋白表达，抑制P13K／Akt等信号通路，导致血管瘤组织细胞的凋亡，而合用IGF-1能抑制雷珠单抗对肺组织的损伤。Objective To explore the efficacy and mechanism of a new monoclonal antibody （ranibizumab） to inhibit the hemangioma of the subcutaneous connective tissue of nude mice, and to study the optimal ratio of drug use. Methods The animal experiment model was successfully set up by hemangioma eells injections. According to the corresponding use without medication, injection of 0. 25, 0. 50 and 0.75 mg/cm^3 ranibizumab, 1 mg/cm^3 pingyangmycin, 0.75 mg/cm^3 ranibizumab ± 10 ng/cm^3 insulin- like growth factors- 1 （IGF- 1 ）, 0. 75 mg/cm^3 ranibizumab ± 30 ng/cm^3 propylene glycol monomethyl ether acetate （PMA）, divided into group A （basis control group） , group B, C, D, group E （ drug control group） , group F （ rezumumab ＋ IGF - 1 ） and group G （ rezmnumab ＋ PMA）. Using histoeytologieal and molecular biological detection methods to verify the efficacy and mechanism. Results After 2 weeks of treatment, the volume of hemangioma was reduced [ group A： （ 171.76 ± 52.46） mm^3, B： （70.85±8.73） mm3, C： （69.84±16.33） mm^3, D： （41.83 ± 18.65） mm^3, E： （61.52 ± 8. 12） mm^3, F： （103.41 ±19.33） mm^3 and G group： （101.19±57.51） mm^3, P=0. 001]. The expression of CD34 and Ki -67 in nude mice was significantly decreased. Except ranibizumab with IGF - 1 group, lung injuries appeared in all others drug treatment groups, while of ranibizulnab treatment groups were lighter than pingyangmyein group. Ranibizumab significantly inhibited the expression of vascular endo- thelial growth factor A （ VEGF - A） protein in nude mice, leading to tissue cell apoptosis. The use of ranibizumab with IGF- 1 can maintain phosphatidylinositol 3 kinase/protein kinase B （PI3K/Akt） signaling pathway, so that can protect lung tissue cells. Conclusion The expression of VEGF - A protein in tumor tissue was inhibited by ranibizumab by blocking the PI3K/Akt signaling pathway, leading to the proliferation of hemangioma cells. While, ranibizumab combined with IGF - 1 can reduce t

关 键 词：血管瘤 血管内皮生长因子 雷珠单抗 类咦岛素生长因子 

分 类 号：R392[医药卫生—免疫学]